While a variety of histiotype-specific tumor antigens have been identified on some human neoplasms, e.g., malignant melanoma, and tumor-specific antibodies readily produced, human colon cancer, the most common neoplasm in this country, has been refractory to such an analysis. There is no unequivocal evidence of tumor-specific antigens on human colorectal cancer cells, although common, tumor-specific antigens have been demonstrated on chemically induced rat colon carcinomas. This application proposes to harness immunological and chemical tools to dissect cell surface components mediating organoid differentiation, inter-cellular adhesion, and tumor specific antigenicity. Cell surface markers will be dissected on human colon cancer cell lines (LS174, LS180 and LS123) as well as their clonal variants, which have been characterized morphologically and by in vitro and in vivo (tumorigenicity) growth. Factors controlling glandular, organoid differentiation, as displayed in hollow fiber culture systems, are dissected by admixing materials derived from appropriate colon cell lines and clones to lines and/or clones which are incapable of displaying this organization. Mediators of organoid differentiation are identified by addition of supernates and/or membrane fractions to the extracapillary compartments of hollow fibers. Inter-cellular adhesive factors are identified by reaggregation in spinner cultures and by formation of multicellular tumor spheroids. Antigenic surface structures distinctive of malignancy are dissected utilizing antibodies, which have already been produced by hybridomas of murine myeloma cell lines with spleen cells from mice immunized with neoplastic lines. Specificity of the monoclonal xenoantibodies is monitored by reactions against normal adult and fetal colonic mucosal cells, normal cells from other tissues, and cancer cells from other neoplasms, particularly those producing CEA. These studies may elucidate cell surface structures critical to the expression of the neoplastic state, which might serve as a focus of immunotherapy.